BRCA1 protein and nucleolin colocalize in breast carcinoma tissue and cancer cell lines

Natalie Tulchin, Monique Chambon, Gloria Juan, Steven Dikman, James Strauchen, Leonard Ornstein, Blase Billack, Nicholas T. Woods, Alvaro N.A. Monteiro

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The breast and ovarian cancer susceptibility gene BRCA1 encodes a tumor suppressor. BRCA1 protein, which is involved in DNA damage response, has been thought to be found primarily in cell nuclei. In the present investigation, immunohistological studies of BRCA1 protein in frozen breast cancer tissue and MCF7 and HeLa cell lines revealed BRCA1 expression in both nucleoli and nucleoplasmic foci. Immunoelectron microscopic studies of estrogen-stimulated MCF7 cells demonstrated BRCA1 protein localization in the granular components of the nucleolus. Moreover, immunofluorescence of BRCA1 and nucleolin double-labeling showed colocalization in both nucleoli and nucleoplasmic foci in breast tumor cells and asynchronously growing MCF7 and HeLa cells. Multiparameter analysis of BRCA1 and nucleolin in relation to cell cycle position (DNA content) showed expression during G1-S and persistence of BRCA1 during G2/M. After γ-irradiation of MCF7 cells, BRCA1 protein dispersed from nucleoli and nucleoplasmic foci to other nucleoplasmic sites, which did not colocalize with nucleolin. Small interfering RNA-mediated knockdown of BRCA1 protein resulted in decreased immunofluorescence staining, which was confirmed by Western blotting. The observed colocalization of BRCA1 and nucleolin raises new possibilities for the nucleoplasmnucleolus pathways of these proteins and their functional significance.

Original languageEnglish (US)
Pages (from-to)1203-1214
Number of pages12
JournalAmerican Journal of Pathology
Volume176
Issue number3
DOIs
Publication statusPublished - Mar 2010

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Tulchin, N., Chambon, M., Juan, G., Dikman, S., Strauchen, J., Ornstein, L., ... Monteiro, A. N. A. (2010). BRCA1 protein and nucleolin colocalize in breast carcinoma tissue and cancer cell lines. American Journal of Pathology, 176(3), 1203-1214. https://doi.org/10.2353/ajpath.2010.081063